Adaptation mechanisms in phosphorylation cycles by allosteric binding and gene autoregulation

Zhou Fang*, Bayu Jayawardhana, Arjan van der Schaft, Chuanhou Gao

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


In this article, we study adaptation mechanisms in a class of phosphorylation cycles where allosteric binding and gene autoregulation mechanisms regulate the phosphorylation processes. We show that both mechanisms enable a robust setpoint regulation of the regulator metabolite in the presence of constant, as well as periodic, external stimuli. The allosteric binding mechanism without the presence of gene autoregulation can serve as an integral controller. Furthermore, we show that the incorporation of a gene autoregulation mechanism enables the gene expression system to act as a genetic oscillator, which allows for the adaptation mechanism to periodic external stimuli. These results provide a theoretical explanation to the cell homeostasis under quasi-constant environmental conditions, as well as periodic, biological rhythms.

Original languageEnglish
Article number8861075
Pages (from-to)3457-3470
Number of pages14
JournalIEEE-Transactions on Automatic Control
Issue number8
Early online date7-Oct-2019
Publication statusPublished - Aug-2020


  • Chemicals
  • Robustness
  • Gene expression
  • Substrates
  • Kinetic theory
  • Oscillators
  • Biological oscillator
  • chemical reaction network
  • gene regulation
  • integral control
  • internal model principle
  • phosphorylation cycles

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